Proteomics: Prediction and Analysis of Protein Networks

We are amongst the first groups to describe how many weak functional genomic features could be systematically integrated with data mining techniques to predict protein networks (comprising protein interactions and other functional linkages). Some of the features integrated were obviously related to protein interactions (e.g. expression correlations) but many others such as (e.g. essentiality) were less so. We have had a number of localization and interaction predictions experimentally verified. In more recent work, we were able to calibrate the degree to which the data quality and the specific mining approach is associated with the strength of the predictions. In addition, we have studied the structure of protein networks, both on a large-scale in terms of global statistics (e.g. the diameter) and on a small-scale in terms of local network motifs (e.g. hubs). In particular, we have correlated network hubs with gene essentiality. Most importantly, we were the first to study the dynamics of regulatory networks. This allowed us to discover changing transient hubs and systematic patterns of connectivity rewiring in the yeast regulatory network. We were able to show for the first time that network dramatically changes in different conditions.

2007 snippet describing some of the lab's work in networks [html] [doc]
early 2009 description of some of the lab's work in networks for a general audience [html] [doc]
early 2009 description of some of the lab's work in networks, referenced, for a more technical audience [html] [doc]

HiC-spector: a matrix library for spectral and reproducibility analysis of Hi-C contact maps.
KK Yan, GG Yardimci, C Yan, WS Noble, M Gerstein (2017). Bioinformatics 33: 2199-2201.

OrthoClust: an orthology-based network framework for clustering data across multiple species.
KK Yan, D Wang, J Rozowsky, H Zheng, C Cheng, M Gerstein (2014). Genome Biol 15: R100.

Interpretation of genomic variants using a unified biological network approach.
E Khurana, Y Fu, J Chen, M Gerstein (2013). PLoS Comput Biol 9: e1002886.

Tcf7 is an important regulator of the switch of self-renewal and differentiation in a multipotential hematopoietic cell line.
JQ Wu, M Seay, VP Schulz, M Hariharan, D Tuck, J Lian, J Du, M Shi, Z Ye, M Gerstein, MP Snyder, S Weissman (2012). PLoS Genet 8: e1002565.

Extensive promoter-centered chromatin interactions provide a topological basis for transcription regulation.
G Li, X Ruan, RK Auerbach, KS Sandhu, M Zheng, P Wang, HM Poh, Y Goh, J Lim, J Zhang, HS Sim, SQ Peh, FH Mulawadi, CT Ong, YL Orlov, S Hong, Z Zhang, S Landt, D Raha, G Euskirchen, CL Wei, W Ge, H Wang, C Davis, KI Fisher-Aylor, A Mortazavi, M Gerstein, T Gingeras, B Wold, Y Sun, MJ Fullwood, E Cheung, E Liu, WK Sung, M Snyder, Y Ruan (2012). Cell 148: 84-98.

Novel insights through the integration of structural and functional genomics data with protein networks.
D Clarke, N Bhardwaj, MB Gerstein (2012). J Struct Biol 179: 320-6.

Systematic control of protein interactions for systems biology.
N Bhardwaj, D Clarke, M Gerstein (2011). Proc Natl Acad Sci U S A 108: 20279-80.

Construction and analysis of an integrated regulatory network derived from high-throughput sequencing data.
C Cheng, KK Yan, W Hwang, J Qian, N Bhardwaj, J Rozowsky, ZJ Lu, W Niu, P Alves, M Kato, M Snyder, M Gerstein (2011). PLoS Comput Biol 7: e1002190.

Integration of protein motions with molecular networks reveals different mechanisms for permanent and transient interactions.
N Bhardwaj, A Abyzov, D Clarke, C Shou, MB Gerstein (2011). Protein Sci 20: 1745-54.

Diverse protein kinase interactions identified by protein microarrays reveal novel connections between cellular processes.
J Fasolo, A Sboner, MG Sun, H Yu, R Chen, D Sharon, PM Kim, M Gerstein, M Snyder (2011). Genes Dev 25: 767-78.

A cis-regulatory map of the Drosophila genome.
N Negre, CD Brown, L Ma, CA Bristow, SW Miller, U Wagner, P Kheradpour, ML Eaton, P Loriaux, R Sealfon, Z Li, H Ishii, RF Spokony, J Chen, L Hwang, C Cheng, RP Auburn, MB Davis, M Domanus, PK Shah, CA Morrison, J Zieba, S Suchy, L Senderowicz, A Victorsen, NA Bild, AJ Grundstad, D Hanley, DM MacAlpine, M Mannervik, K Venken, H Bellen, R White, M Gerstein, S Russell, RL Grossman, B Ren, JW Posakony, M Kellis, KP White (2011). Nature 471: 527-31.

Measuring the evolutionary rewiring of biological networks.
C Shou, N Bhardwaj, HY Lam, KK Yan, PM Kim, M Snyder, MB Gerstein (2011). PLoS Comput Biol 7: e1001050.

Rewiring of transcriptional regulatory networks: hierarchy, rather than connectivity, better reflects the importance of regulators.
N Bhardwaj, PM Kim, MB Gerstein (2010). Sci Signal 3: ra79.

Extensive in vivo metabolite-protein interactions revealed by large-scale systematic analyses.
X Li, TA Gianoulis, KY Yip, M Gerstein, M Snyder (2010). Cell 143: 639-50.

Analysis of combinatorial regulation: scaling of partnerships between regulators with the number of governed targets.
N Bhardwaj, MB Carson, A Abyzov, KK Yan, H Lu, MB Gerstein (2010). PLoS Comput Biol 6: e1000755.

MOTIPS: automated motif analysis for predicting targets of modular protein domains.
HY Lam, PM Kim, J Mok, R Tonikian, SS Sidhu, BE Turk, M Snyder, MB Gerstein (2010). BMC Bioinformatics 11: 243.

Comparing genomes to computer operating systems in terms of the topology and evolution of their regulatory control networks.
KK Yan, G Fang, N Bhardwaj, RP Alexander, M Gerstein (2010). Proc Natl Acad Sci U S A 107: 9186-91.

Analysis of membrane proteins in metagenomics: networks of correlated environmental features and protein families.
PV Patel, TA Gianoulis, RD Bjornson, KY Yip, DM Engelman, MB Gerstein (2010). Genome Res 20: 960-71.

Network modeling identifies molecular functions targeted by miR-204 to suppress head and neck tumor metastasis.
Y Lee, X Yang, Y Huang, H Fan, Q Zhang, Y Wu, J Li, R Hasina, C Cheng, MW Lingen, MB Gerstein, RR Weichselbaum, HR Xing, YA Lussier (2010). PLoS Comput Biol 6: e1000730.

Analysis of diverse regulatory networks in a hierarchical context shows consistent tendencies for collaboration in the middle levels.
N Bhardwaj, KK Yan, MB Gerstein (2010). Proc Natl Acad Sci U S A 107: 6841-6.

Improved reconstruction of in silico gene regulatory networks by integrating knockout and perturbation data.
KY Yip, RP Alexander, KK Yan, M Gerstein (2010). PLoS One 5: e8121.

mRNA expression profiles show differential regulatory effects of microRNAs between estrogen receptor-positive and estrogen receptor-negative breast cancer.
C Cheng, X Fu, P Alves, M Gerstein (2009). Genome Biol 10: R90.

Multi-level learning: improving the prediction of protein, domain and residue interactions by allowing information flow between levels.
KY Yip, PM Kim, D McDermott, M Gerstein (2009). BMC Bioinformatics 10: 241.

Understanding modularity in molecular networks requires dynamics.
RP Alexander, PM Kim, T Emonet, MB Gerstein (2009). Sci Signal 2: pe44.

Integrated assessment of genomic correlates of protein evolutionary rate.
Y Xia, EA Franzosa, MB Gerstein (2009). PLoS Comput Biol 5: e1000413.

Training set expansion: an approach to improving the reconstruction of biological networks from limited and uneven reliable interactions.
KY Yip, M Gerstein (2009). Bioinformatics 25: 243-50.

The role of disorder in interaction networks: a structural analysis.
PM Kim, A Sboner, Y Xia, M Gerstein (2008). Mol Syst Biol 4: 179.

An integrated system for studying residue coevolution in proteins.
KY Yip, P Patel, PM Kim, DM Engelman, D McDermott, M Gerstein (2008). Bioinformatics 24: 290-2.

Positive selection at the protein network periphery: evaluation in terms of structural constraints and cellular context.
PM Kim, JO Korbel, MB Gerstein (2007). Proc Natl Acad Sci U S A 104: 20274-9.

Comparing classical pathways and modern networks: towards the development of an edge ontology.
LJ Lu, A Sboner, YJ Huang, HX Lu, TA Gianoulis, KY Yip, PM Kim, GT Montelione, MB Gerstein (2007). Trends Biochem Sci 32: 320-31.

Total ancestry measure: quantifying the similarity in tree-like classification, with genomic applications.
H Yu, R Jansen, G Stolovitzky, M Gerstein (2007). Bioinformatics 23: 2163-73.

Getting connected: analysis and principles of biological networks.
X Zhu, M Gerstein, M Snyder (2007). Genes Dev 21: 1010-24.

The importance of bottlenecks in protein networks: correlation with gene essentiality and expression dynamics.
H Yu, PM Kim, E Sprecher, V Trifonov, M Gerstein (2007). PLoS Comput Biol 3: e59.

Relating three-dimensional structures to protein networks provides evolutionary insights.
PM Kim, LJ Lu, Y Xia, MB Gerstein (2006). Science 314: 1938-41.

An integrative genomic approach to uncover molecular mechanisms of prokaryotic traits.
Y Liu, J Li, L Sam, CS Goh, M Gerstein, YA Lussier (2006). PLoS Comput Biol 2: e159.

The tYNA platform for comparative interactomics: a web tool for managing, comparing and mining multiple networks.
KY Yip, H Yu, PM Kim, M Schultz, M Gerstein (2006). Bioinformatics 22: 2968-70.

Genomic analysis of the hierarchical structure of regulatory networks.
H Yu, M Gerstein (2006). Proc Natl Acad Sci U S A 103: 14724-31.

Design principles of molecular networks revealed by global comparisons and composite motifs.
H Yu, Y Xia, V Trifonov, M Gerstein (2006). Genome Biol 7: R55.

Global landscape of protein complexes in the yeast Saccharomyces cerevisiae.
NJ Krogan, G Cagney, H Yu, G Zhong, X Guo, A Ignatchenko, J Li, S Pu, N Datta, AP Tikuisis, T Punna, JM Peregrin-Alvarez, M Shales, X Zhang, M Davey, MD Robinson, A Paccanaro, JE Bray, A Sheung, B Beattie, DP Richards, V Canadien, A Lalev, F Mena, P Wong, A Starostine, MM Canete, J Vlasblom, S Wu, C Orsi, SR Collins, S Chandran, R Haw, JJ Rilstone, K Gandi, NJ Thompson, G Musso, P St Onge, S Ghanny, MH Lam, G Butland, AM Altaf-Ul, S Kanaya, A Shilatifard, E O'Shea, JS Weissman, CJ Ingles, TR Hughes, J Parkinson, M Gerstein, SJ Wodak, A Emili, JF Greenblatt (2006). Nature 440: 637-43.

Predicting interactions in protein networks by completing defective cliques.
H Yu, A Paccanaro, V Trifonov, M Gerstein (2006). Bioinformatics 22: 823-9.

Target hub proteins serve as master regulators of development in yeast.
AR Borneman, JA Leigh-Bell, H Yu, P Bertone, M Gerstein, M Snyder (2006). Genes Dev 20: 435-48.

Integrated prediction of the helical membrane protein interactome in yeast.
Y Xia, LJ Lu, M Gerstein (2006). J Mol Biol 357: 339-49.

Inferring Protein-Protein Interactions Using Interaction Network Topologies
A Paccanaro, V Trifonov, H Yu, M Gerstein (2005). International Joint Conference on Neural Networks (IJCNN, Jul. 31-Aug. 4, Montreal, Canada), pages 161 - 166, vol. 1

Protein Interaction Prediction by Integrating Genomic Features and Protein Interaction Network Analysis
LJ Lu, Y Xia, H Yu, A Rives, H Lu, F Schubert, M Gerstein (2005). Data Analysis and Visualization in Genomics and Proteomics (Wiley, NY)

Global analysis of protein phosphorylation in yeast.
J Ptacek, G Devgan, G Michaud, H Zhu, X Zhu, J Fasolo, H Guo, G Jona, A Breitkreutz, R Sopko, RR McCartney, MC Schmidt, N Rachidi, SJ Lee, AS Mah, L Meng, MJ Stark, DF Stern, C De Virgilio, M Tyers, B Andrews, M Gerstein, B Schweitzer, PF Predki, M Snyder (2005). Nature 438: 679-84.

PubNet: a flexible system for visualizing literature derived networks.
SM Douglas, GT Montelione, M Gerstein (2005). Genome Biol 6: R80.

Assessing the limits of genomic data integration for predicting protein networks.
LJ Lu, Y Xia, A Paccanaro, H Yu, M Gerstein (2005). Genome Res 15: 945-53.

Information assessment on predicting protein-protein interactions.
N Lin, B Wu, R Jansen, M Gerstein, H Zhao (2004). BMC Bioinformatics 5: 154.

Genomic analysis of regulatory network dynamics reveals large topological changes.
NM Luscombe, MM Babu, H Yu, M Snyder, SA Teichmann, M Gerstein (2004). Nature 431: 308-12.

Structure and evolution of transcriptional regulatory networks.
MM Babu, NM Luscombe, L Aravind, M Gerstein, SA Teichmann (2004). Curr Opin Struct Biol 14: 283-91.

Analyzing cellular biochemistry in terms of molecular networks.
Y Xia, H Yu, R Jansen, M Seringhaus, S Baxter, D Greenbaum, H Zhao, M Gerstein (2004). Annu Rev Biochem 73: 1051-87.

Annotation transfer between genomes: protein-protein interologs and protein-DNA regulogs.
H Yu, NM Luscombe, HX Lu, X Zhu, Y Xia, JD Han, N Bertin, S Chung, M Vidal, M Gerstein (2004). Genome Res 14: 1107-18.

Genomic analysis of essentiality within protein networks.
H Yu, D Greenbaum, H Xin Lu, X Zhu, M Gerstein (2004). Trends Genet 20: 227-31.

TopNet: a tool for comparing biological sub-networks, correlating protein properties with topological statistics.
H Yu, X Zhu, D Greenbaum, J Karro, M Gerstein (2004). Nucleic Acids Res 32: 328-37.

A map of the interactome network of the metazoan C. elegans.
S Li, CM Armstrong, N Bertin, H Ge, S Milstein, M Boxem, PO Vidalain, JD Han, A Chesneau, T Hao, DS Goldberg, N Li, M Martinez, JF Rual, P Lamesch, L Xu, M Tewari, SL Wong, LV Zhang, GF Berriz, L Jacotot, P Vaglio, J Reboul, T Hirozane-Kishikawa, Q Li, HW Gabel, A Elewa, B Baumgartner, DJ Rose, H Yu, S Bosak, R Sequerra, A Fraser, SE Mango, WM Saxton, S Strome, S Van Den Heuvel, F Piano, J Vandenhaute, C Sardet, M Gerstein, L Doucette-Stamm, KC Gunsalus, JW Harper, ME Cusick, FP Roth, DE Hill, M Vidal (2004). Science 303: 540-3.

Reconstructing genetic networks in yeast.
Z Zhang, M Gerstein (2003). Nat Biotechnol 21: 1295-7.

A Bayesian networks approach for predicting protein-protein interactions from genomic data.
R Jansen, H Yu, D Greenbaum, Y Kluger, NJ Krogan, S Chung, A Emili, M Snyder, JF Greenblatt, M Gerstein (2003). Science 302: 449-53.

Prediction of regulatory networks: genome-wide identification of transcription factor targets from gene expression data.
J Qian, J Lin, NM Luscombe, H Yu, M Gerstein (2003). Bioinformatics 19: 1917-26.

Genomic analysis of gene expression relationships in transcriptional regulatory networks.
H Yu, NM Luscombe, J Qian, M Gerstein (2003). Trends Genet 19: 422-7.

Relating whole-genome expression data with protein-protein interactions.
R Jansen, D Greenbaum, M Gerstein (2002). Genome Res 12: 37-46.

Proteomics. Integrating interactomes.
M Gerstein, N Lan, R Jansen (2002). Science 295: 284-7.

Integration of genomic datasets to predict protein complexes in yeast.
R Jansen, N Lan, J Qian, M Gerstein (2002). J Struct Funct Genomics 2: 71-81.

Bridging structural biology and genomics: assessing protein interaction data with known complexes.
AM Edwards, B Kus, R Jansen, D Greenbaum, J Greenblatt, M Gerstein (2002). Trends Genet 18: 529-36.

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